Following birth, dogs and sheep show a rapid decline in blood hemoglobin concentration which is defined as postnatal anemia. In the dog, we have shown that the total hemoglobin does not change during this period, however, the rapid growth of the animal including its vascular system, causes a drop in hemoglobin concentration. There is a change in hemoglobin function effectively allowing a given quantities of hemoglobin to transport more oxygen. This change in function is mediated by an intracellular increase in 2,3-diphosphoglycerate concentration in neonatal dog erythrocytes. The sheep shows a much more transient change in intracellular 2,3-diphosphoglycerate concentrations. The sheep differs from the dog in that there is a postnatal shift from a fetal hemoglobin to an adult hemoglobin and neither hemoglobin interacts directly with 2,3-diphosphoglycerate. Any effect of 2,3-diphosphoglycerate seems to be due to a reduction in intracellular pH. The postnatal changes in 2,3-diphosphoglycerate do not appear to be due to alteration in pyruvate kinase activity. We are examining other components of the glycolytic pathway to determine the nature of the 2,3-diphosphoglycerate regulation in the sheep.